Konstantinos Dafopoulos

Prognostic value of follicular fluid 25-OH vitamin D and glucose levels in the IVF outcome

ObjectivesThe aim of the present study was to measure serum and follicular fluid 25-OH vitamin D and glucose levels in women who underwent IVF-ET treatment and to further investigate whether the circulating 25-OH vitamin D and glucose levels correlate with IVF success.MethodsThis prospective observational study included 101 consecutive women who underwent 101 IVF-ICSI ovarian stimulation cycles and were allocated to one of the three groups according to their follicular fluid 25-OH vitamin D concentrations. Group A (n = 31) with less than 20 ng/ml, group B (n = 49) with vitamin levels between 20.1 and 30 ng/ml and group C (n = 21) with more than 30 ng/ml vitamin concentration.ResultsFollicular fluid vitamin levels significantly correlated with the quality of embryos in total (r = -0.27, p = 0.027), while the quality of embryos of group C were of lower quality as compared to those of groups A and B (p = 0.009). Follicular fluid glucose levels were lower in women of group C as compared to the respective levels of groups A and B (p = 0.003). Clinical pregnancy rate demonstrated in 14.5% in women of group C and 32.3% and 32.7% in groups A and B, respectively (p = 0.047).ConclusionThe data suggests that excess serum and follicular fluid vitamin levels in combination with decreased follicular fluid glucose levels have a detrimental impact on the IVF outcome.

Impact of Maternal Diabetes on Epigenetic Modifications Leading to Diseases in the Offspring

Gestational diabetes, occurring during the hyperglycemic period of pregnancy in maternal life, is a pathologic state that increases the incidence of complications in both mother and fetus. Offspring thus exposed to an adverse fetal and early postnatal environment may manifest increased susceptibility to a number of chronic diseases later in life. Compelling evidence for the role of epigenetic transmission in these complications has come from comparison of siblings born before and after the development of maternal diabetes, exposure to this intrauterine diabetic environment being shown to cause alterations in fetal growth patterns which predispose these infants to developing overweight and obesity later in life. Diabetes of the offspring is also mainly the consequence of exposure to the diabetic intrauterine environment, in addition to genetic susceptibility. Since obesity and diabetes are known to increase the risk of cardiovascular disease, cardiovascular sequelae in the offspring of diabetic mothers are virtually inevitable. Research data also suggest that exposure to a diabetic intrauterine environment during pregnancy is associated with an increase in dyslipidemia, subclinical vascular inflammation, and endothelial dysfunction processes in the offspring, all of which are linked with development of cardiovascular disease later in life. The main underlying mechanisms involve persistent hyperglycemia hyperinsulinemia and leptin resistance.

Blood ghrelin, resistin, and adiponectin concentrations during the normal menstrual cycle

OBJECTIVE To investigate changes of ghrelin, resistin, and adiponectin levels in the circulation during the normal menstrual cycle. DESIGN Longitudinal study. SETTING The study was conducted at a university hospital. PATIENT(S) Eight healthy normally cycling women. INTERVENTION(S) The women were observed during a whole menstrual cycle. Daily blood samples were taken every morning, after overnight fasting, from day 2 of the cycle until the next menstrual period. MAIN OUTCOME MEASURE(S) Plasma acylated and unacylated ghrelin and serum resistin, adiponectin, FSH, LH, E(2), and P levels were measured in all blood samples. RESULT(S) In all women serum FSH, LH, E(2), and P levels, normalized to the midcycle peak LH value, showed the typical changes of the normal menstrual cycle. Acylated and unacylated ghrelin, resistin, and adiponectin levels did not change significantly during the whole menstrual cycle. CONCLUSION(S) The present study shows for the first time that plasma ghrelin and serum resistin levels do not change significantly during the normal menstrual cycle. It is also confirmed that serum adiponectin levels remain stable throughout the cycle. It is suggested that ovarian steroid dynamics during the cycle have no effect on the secretion of these substances.

Role of Adipokines and Other Inflammatory Mediators in Gestational Diabetes Mellitus and Previous Gestational Diabetes Mellitus

Previous Gestational Diabetes Mellitus (pGDM) is a common condition and has been associated with future development of Type 2 Diabetes Mellitus (T2DM) and Metabolic Syndrome (MS) in women affected. The pathogenesis and risk factors implicated in the development of these conditions later in the lives of women with pGDM are not as yet fully understood. Research has recently focused on a group of substances produced mainly by adipose tissue called adipokines, this group including, among others, adiponectin, leptin, Retinol-Binding Protein-4 (RBP-4), and resistin. These substances as well as other inflammatory mediators (CRP, IL-6, PAI-1, TNF-α) seem to play an important role in glucose tolerance and insulin sensitivity dysregulation in women with pGDM. We summarize the data available on the role of these molecules.

Effect of ghrelin on gonadotrophin secretion in women during the menstrual cycle

BACKGROUND It has been suggested that ghrelin may affect reproduction in animals by decreasing pituitary LH secretion. The role of ghrelin on LH secretion in women has not been investigated. Our aim was to assess the effect of ghrelin administration on basal and GnRH-induced LH secretion during the menstrual cycle. METHODS Normally cycling women (n = 10) received on Day 3 of three consecutive cycles a single bolus i.v. of either ghrelin (1 microg/kg, cycle 1) or GnRH (100 microg, cycle 2) or GnRH plus ghrelin (cycle 3). In cycle 1, ghrelin was also injected in late follicular and mid-luteal phase of the cycle. Saline was injected in a preceding cycle (cycle 1, control). Blood samples were taken before drugs or saline injection (time 0) as well as at -15, 15, 30, 45, 60, 75, 90 and 120 min. RESULTS Plasma ghrelin levels increased rapidly, peaking at 15 or 30 min (P < 0.001), then decreased steadily, approaching pre-injection levels at 120 min. Serum FSH, LH, estradiol and progesterone levels remained unchanged. The stimulating effect of GnRH on LH and FSH secretion was unaffected by ghrelin injection. In contrast to saline, ghrelin stimulated a significant increase in growth hormone levels. CONCLUSIONS Under these experimental conditions, our results demonstrate for the first time the inability of a bolus of ghrelin to affect basal and GnRH-induced LH and FSH secretion. It is suggested that ghrelin does not play a major physiological role in gonadotrophin secretion in women.

Effect of ovarian hormones on serum adiponectin and resistin concentrations

OBJECTIVE To investigate the effect of ovarian hormones on adiponectin and resistin levels in women. DESIGN Experimental study. SETTING University hospital. PATIENT(S) Thirteen normally cycling women (7 in group 1 and 6 in group 2) and 8 postmenopausal women (group 3). INTERVENTION(S) Women of group 1 were investigated in a control cycle and in a subsequent cycle in which total abdominal hysterectomy plus bilateral salpingooophorectomy (TAH+BSO) was performed on day 3. In both cycles, the women received increasing doses of E(2) from days 3 to 5. Women of group 2 underwent TAH+BSO on day 3 without receiving any hormonal treatment. Women of group 3 received increasing doses of E(2) for 15 days. MAIN OUTCOME MEASURE(S) Adiponectin, resistin, and E(2) concentrations. RESULT(S) In group 1, serum adiponectin and resistin levels did not show any significant changes for the week following day 3 and were similar in the two cycles. In group 2, adiponectin and resistin levels were similar before and after TAH+BSO and remained stable during the first postoperative week. In group 3, no significant changes in adiponectin and resistin levels were seen during the 15 days of E(2) administration. CONCLUSION(S) Adiponectin and resistin values were not affected either by estrogen treatment or after ovariectomy in women. It is suggested that ovarian hormones are not involved in the regulation of adiponectin and resistin secretion in women.

The impact of cigarette smoking and alcohol consumption on sperm parameters and sperm DNA fragmentation (SDF) measured by Halosperm(

PurposeBoth cigarette smoking and alcohol consumption are somehow implicated in sperm function, but the impact of these two lifestyle factors on sperm parameters remains controversial. The present study is focused on the impact of cigarette smoking and alcohol consumption separately and combined on sperm parameters and sperm DNA fragmentation (SDF).MethodsThe study included 207 consecutive semen samples derived from men who were seeking semen analysis for fertility purposes in our IVF Unit.ResultsSemen volume, percent of degenerated spermatozoa and SDF were significantly correlated with the various smoking status. The percent of spermatozoa with small halos significantly correlated with the alcohol status. The smoking status of the men was correlated with the alcohol status.ConclusionsCigarette smoking and alcohol consumption separately and combined were found to have deleterious effect on sperm parameters and SDF. It is suggested that both habits may contribute to infertility problems.

Osteoprotegerin as a Marker of Atherosclerosis in Diabetic Patients

Atherosclerosis is the principal cause of cardiovascular disease (CVD) and has many risk factors, among which is diabetes. Osteoprotegerin (OPG) is a soluble glycoprotein, involved in bone metabolism. OPG is also found in other tissues, and studies have shown that it is expressed in vascular smooth muscle cells. OPG has been implicated in various inflammations and also has been linked to diabetes mellitus. Increased serum OPG levels were found in patients with diabetes and poor glycemic control. Furthermore, prepubertal children with type 1 diabetes have significantly increased OPG levels. Receptor activator of nuclear factor kappa-B ligand (RANKL) is not found in the vasculature in normal conditions, but may appear in calcifying areas. OPG and RANKL are important regulators of mineral metabolism in both bone and vascular tissues. Few data are available on the relationship between plasma OPG/RANKL levels and endothelial dysfunction as assessed using noninvasive methods like ultrasound indexes, neither in the general population nor, more specifically, in diabetic patients. The aim of our review study was to investigate, based on the existing data, these interrelationships in order to identify a means of predicting, via noninvasive methods, later development of endothelial dysfunction and vascular complications in diabetic patients.

Elimination Half-Life of Anti-Müllerian Hormone

CONTEXT Anti-Müllerian hormone (AMH) is a glycoprotein that is secreted by the granulosa cells in the human ovary. In the postpubertal female, circulating AMH reflects the number of follicles within the ovary. It is mandatory to know the serum elimination half-life (t(1/2)) of AMH to study in vivo short-term changes of the hormone. OBJECTIVE Our objective was to determine the kinetics of decay of AMH in the human female. PATIENTS, DESIGN, AND SETTING Premenopausal women undergoing total abdominal hysterectomy plus bilateral salpingo-oophorectomy participated in this cohort study (n = 21) at an academic tertiary referral center. INTERVENTIONS Serum samples were obtained immediately before surgery and in 12-h intervals thereafter for 8 d. MAIN OUTCOME MEASURE AMH elimination was calculated, applying a one-compartment model with first-order kinetics. RESULTS Mean preoperative AMH levels were 0.67 ng/ml (range, 0.1-1.78 ng/ml) and dropped to 0.08 ng/ml within 84 h after surgery. The AMH decay followed first-order kinetics. The mean terminal t(1/2) of AMH was calculated as 27.6 ± 0.8 h. CONCLUSION AMH elimination reaches approximately 84% after 3 d, approximately 91% after 4 d, approximately 95% after 5 d, and can be considered complete after 8 d.

Factors affecting outcome after ICSI with spermatozoa retrieved from cryopreserved testicular tissue in non-obstructive azoospermia

There is a lack of data regarding variables affecting the treatment outcome for non-obstructive azoospermia when spermatozoa from cryopreserved testicular specimens are utilized for ICSI. The objective of the present retrospective analysis was to investigate the effect of various parameters on treatment outcome in such cases. One hundred and sixty-five couples with non-obstructive azoospermic males undergoing a total of 297 cycles were included. In all cases the testicular tissue retrieved by multiple open-biopsy testicular sperm extraction was stored in liquid nitrogen and, after thawing, only mature spermatozoa were used for ICSI. When no motile spermatozoa were recovered, immotile spermatozoa were used. In 159 cycles, motile spermatozoa were utilized for ICSI, while in 138 cycles immotile spermatozoa were utilized. Higher normal fertilization rate (60.4 +/- 3.1 versus 51.3 +/- 1.6%, P < 0.05), number of embryos transferred (2.8 +/- 0.06 versus 2.6 +/- 0.04, P < 0.05), modified cumulative embryo score (31.2 +/- 1.6 versus 23.9 +/- 0.8, P < 0.001), and proportion of motile spermatozoa injected (67.8 versus 49.8%, P < 0.05) were observed in cycles that resulted in clinical pregnancies. Binary logistic regression analysis showed that sperm motility (odds ratio 2.06, 95% CI 1.1-3.9, P < 0.05), but not womans age, number of treatment cycle, type of GnRH-analogue used for pituitary suppression, number of oocytes retrieved or number of embryos transferred was a significant determinant of the likelihood of clinical pregnancy. In conclusion, sperm motility after freeze/thawing of testicular tissue is the major determinant of the success of ICSI in non-obstructive azoospermia.